title: Apigenin inhibits the GLUT-1 glucose transporter and the phosphoinositide 3-kinase/Akt pathway in human pancreatic cancer cells.
abstract: OBJECTIVE
  The antiproliferative mechanisms of flavonoid drugs inpancreatic cancer cells remain unclear. In this study, we evaluated the effects of the flavonoid apigenin on glucose uptake, on the expression of the glucose transporter 1 (GLUT-1), and on the phosphoinositide 3-kinase (PI3K)/Akt pathway in human pancreatic cancer cells.
  
  
  METHODS
  Human pancreatic cancer cells were treated with apigenin and then underwent glucose uptake assays. Real-time reverse transcription-polymerase chain reaction and Western blot analysis were conducted to evaluate GLUT-1 and pAkt expression in CD18 and S2-013 human pancreatic cancer cells after treatment with apigenin or PI3K inhibitors (LY294002 and wortmannin).
  
  
  RESULTS
  Apigenin (0-100 microM) significantly inhibited, in a dose-dependent fashion, glucose uptake in CD18 and S2-013 human pancreatic cancer cell lines. Apigenin inhibited both GLUT-1 mRNA and protein expression in a concentration- and time-dependent fashion. The PI3K inhibitors, like apigenin, downregulated both GLUT-1 mRNA and protein expression.
  
  
  CONCLUSIONS
  Our results demonstrate that the flavonoid apigenin decreases glucose uptake and downregulates the GLUT-1 glucose transporter in human pancreatic cancer cells. In addition, the inhibitory effects of apigenin and the PI3K inhibitors on GLUT-1 are similar, indicating that the PI3K/Akt pathway is involved in mediating apigenin's effects on downstream targets such as GLUT-1.
authors.affiliation: Departments of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. lgolkar@hotmail.com
authors.forename: Laleh G
authors.initials: LG
authors.lastname: Melstrom
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Salabat
authors.forename: Xian-Zhong
authors.initials: XZ
authors.lastname: Ding
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Milam
authors.forename: Matthew
authors.initials: M
authors.lastname: Strouch
authors.forename: Jill C
authors.initials: JC
authors.lastname: Pelling
authors.forename: David J
authors.initials: DJ
authors.lastname: Bentrem
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D051272:Glucose Transporter Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D047310:Apigenin; D051017:Apoptosis Regulatory Proteins; D051272:Glucose Transporter Type 1; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C486377:AKTIP protein, human; C495677:SLC2A1 protein, human